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Orexin A presynaptically decreases inhibitory synaptic transmission in rat locus coeruleus neurons

Kargar, HM-P; Azizi, H; Mirnajafi-Zadeh, J; Mani, AR; Semnaniann, S; (2018) Orexin A presynaptically decreases inhibitory synaptic transmission in rat locus coeruleus neurons. Neuroscience Letters , 683 pp. 89-93. 10.1016/j.neulet.2018.06.022. Green open access

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Abstract

Locus coeruleus nucleus (LC) is a major noradrenergic nucleus in the brain. It receives dense orexinergic projections from lateral hypothalamus. Whilst it is known that orexin A increases firing rate of LC neurons, its effect on spontaneous and evoked inhibitory postsynaptic currents (sIPSCs and eIPSCs, respectively) has not been yet identified. In this research, we investigated the effect of orexin A on eIPSCs and sIPSCs in LC neurons. Whole-cell recordings revealed that orexin A suppresses eIPSCs amplitude in which this effect was blocked by an orexin type-1 receptors antagonist (SB-334867) and cannabinoid type-1 (CB1) receptors antagonist (AM251). Moreover, exposure of neurons to BAPTA (Ca2+ chelator) and U73122 (phospholipase C inhibitor) prevented orexin A-induced eIPSCs depression. On the other hand, orexin A increased pair pulse ratio and sIPSCs frequency but had no effect on sIPSCs amplitude. Our results revealed that eIPSCs suppression in the LC is mediated by CB1 receptor through a presynaptic mechanism.

Type: Article
Title: Orexin A presynaptically decreases inhibitory synaptic transmission in rat locus coeruleus neurons
Location: Ireland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neulet.2018.06.022
Publisher version: https://doi.org/10.1016/j.neulet.2018.06.022
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: AM251, Locus coeruleus nucleus, Orexin A, SB-334867, eIPSC, patch clamp recording, sIPSC
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education
URI: https://discovery.ucl.ac.uk/id/eprint/10051844
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